Antidepressants

Abstract

Antidepressants have made major contributions towards the treatment of anxiety and mood disorders. A variety of pharmacologic classes of these agents emerged since the 1960s. Tricyclics and monoamine oxidase inhibitors were early agents developed and remain in use today. Plasma concentration monitoring for therapeutic effects were initiated with the tricyclic agents. However, safety concerns persisted with these agents and the selective serotonin reuptake inhibitors (SSRIs) arose. Since the introduction of the SSRIs, these agents became the foremost prescribed medications for depression and anxiety disorders. The SSRIs have also expanded the understanding of cytochrome P450 (CYP) metabolism, drug transporters, and drug-drug interaction mechanisms. Serotonin norepinephrine reuptake inhibitors (SNRIs) joined the SSRIs but with a dual pharmacologic mechanism of action. Various other pharmacologic types of antidepressants have been fostered such as bupropion, vilazodone, mirtazapine, and vortioxetine. Persons with polymorphic CYP metabolism (e.g., poor or ultrarapid metabolizers) may explain the occurrence of adverse events despite modest drug dosages or the lack of efficacy regardless of the appropriate doses. Pharmacokinetic and pharmacodynamics studies have been conducted for all the antidepressants, exploring the potential association of plasma concentrations with therapeutic outcomes (efficacy and toxicity) but routine therapeutic drug monitoring (TDM) is only recommended for a few agents. There is reason to believe, however, that the incorporation of pharmacogenetic information with TDM practices may ultimately lead to enhanced efficacy, reduced toxicity, and minimized risk for drug interactions.